Pharmaceutical powder cartridge, and inhaler equipped with same

ABSTRACT

To improve administration of powdered pharmaceuticals, a pharmaceutical powder cartridge ( 1 ) for powder inhalers for holding a pharmaceutical depot for a large number of pharmaceutical powder doses is proposed, having at least one storage space ( 6 ) and an integrated metering device, said integrated metering device comprising at least one metering slide ( 9, 13, 14 ) which can be moved approximately transversely in a metering slide channel ( 12 ) at least from a filling position to an emptying position, approximately transversely with respect to the direction of flow of the pharmaceutical powder out from the at least one storage space ( 6 ), said metering slide channel ( 12 ) with the at least one metering slide ( 9, 13, 14 ) being sealed off from the environment at least in the filling position of the metering slide ( 9, 13, 14 ), and also further measures and a corresponding inhaler.

CROSS-REFERENCE TO RELATED APPLICATIONS

This is a Divisional of U.S. patent application Ser. No. 10/348,874 nowU.S. Pat. No. 7,258,118 filed Jan. 22, 2003, which is a non-provisionalof U.S. Provisional Patent Application Ser. No. 60/351,548, filed onJan. 24, 2002, the disclosures of which are both hereby expresslyincorporated by reference herein.

The invention relates to a pharmaceutical powder cartridge for powderinhalers for holding a pharmaceutical depot for a large number ofpharmaceutical powder doses, having at least one storage space and anintegrated metering device, said integrated metering device comprisingat least one metering slide which can be moved approximatelytransversely in a metering slide channel at least from a fillingposition to an emptying position, approximately transversely withrespect to the direction of flow of the pharmaceutical powder out fromthe at least one storage space, and an inhaler equipped accordingly.

BACKGROUND OF THE INVENTION

In the field of treatment of bronchial diseases, and also of otherdiseases in which medication can be given via the airways, it is knownnot only to atomize solutions or suspensions into inhalable aerosols butalso to administer powdered medicaments. Many examples of suchmedicaments are described in the literature, and of these we referpurely by way of illustration to WO 93/11773, EP 0 416 950 A1 and EP 0416 951 A1.

A customary form of administration in this connection is delivery via aninhalation device (inhaler).

Known inhalers for powdered pharmaceuticals include those foradministration of a single dose and also inhalation devices which have astorage space for a plurality of pharmaceutical doses. In connectionwith the latter, it is known either to provide separate storage spacesfor each individual dose or to provide one single receiving space forreceiving a multiplicity of doses of a medicament.

Known inhalers in which a large number of individual doses are providedin separate storage spaces include those in which individual areas ofthe inhaler are each filled with a pharmaceutical dose. An example ofsuch an inhaler is described in U.S. Pat. No. 5,301,666 A. However, itis also known to accommodate a large number of pharmaceutical powderdoses in separate areas of what are called blister packs. An example ofsuch a blister pack for use with an inhaler is described in DE 44 00 083C2. Such a blister pack, which is designed at the same time as adisposable inhaler, is described for example in DE 44 00 084 A1.

An inhalation device into which blister packs can be inserted, whicheach have separate storage spaces for individual doses of a powderedpharmaceutical and which can be emptied one after another with the aidof the inhalation device, is described, for example, in DE 195 23 516C1.

Many examples of inhalers with a storage space for a large number ofpharmaceutical doses are described in the prior art. One example with anexchangeable storage container is described in German PatentSpecification 846 770, and another in WO 95/31237.

An important problem with inhalation systems in which a large number ofdoses of a medically active substance are accommodated in a commonstorage space concerns the apportioning of an individual dose for oneindividual inhalation. In this connection, a great many solutions havebeen proposed, for example those which are described in U.S. Pat. No.2,587,215 A and U.S. Pat. No. 4,274,403 A. Other types of arrangementsfor metering an individual dose of pharmaceutical powder from a storagespace for a large number of pharmaceutical doses are furthermoredescribed in WO 92/09322, WO 93/16748 and DE 35 35 561 C2 and in GB 2165 159 A. An exchangeable cartridge for receiving a large number ofdoses of a pharmaceutical powder with an integrated metering slide isknown from DE 195 22 415 A1.

Another important problem with inhalation of pharmaceutical powdersconcerns the breakdown of the galenic powder formulations into particleswhich can access the lungs. The active substances administered in thisway are generally combined with vehicles in order to achieve areasonable dosing capacity of the medically active substance and to setfurther properties of the pharmaceutical powder, which for example caninfluence the storage life.

Proposed solutions concerning the designs of powder inhalers with whichparticles which can access the lungs are intended to be made availablein an air stream for inhalation are described for example in EP 0 640354 A2, U.S. Pat. No. 5,505,196 A, U.S. Pat. No. 5,320,714 A, U.S. Pat.No. 5,435,301 A, U.S. Pat. No. 5,301,666 A, DE 195 22 416 A1 and WO97/00703. Proposals are also known to use auxiliary energy to generatethe air stream, for example in ZA-A 916741.

In the use of medicaments for inhalation in powder form, it is alsoquite generally known to combine active substances by administeringprepared active substance mixtures. Corresponding proposals are found inEP 0 416 951 A1 and WO 93/11773, for example for combination ofsalmeterol and fluticasone or formoterol and budesonide.

WO 00/74754 and many other publications over a period of more thantwenty years have described how, particularly in powder inhalers, thereis a considerable problem with moisture. Not only can moisture have adisadvantageous effect on the pharmaceutically active composition of themedicament, it can also impair in particular the interplay of physicaland chemical parameters of the combination of active substance andauxiliaries. As a result, lumps may form, for example, or the breakdownof the inhaled powder into particles which can access the lungs may beimpaired. All these circumstances can lead to problems affecting themetering and the efficacy of the administration of a powderedmedicament.

To minimize these disadvantages, various attempts have already been madein the past to reduce the penetration of moisture into a powder inhalerby using seals. Attempts have also been made to reduce thedisadvantageous effects of penetrated moisture by providing desiccantsto absorb the moisture, in particular to keep the air moisture instorage chambers to a minimum.

PRIOR ART

In the prior art, WO 00/74754 expressly describes how attempts to solvethis problem have generally been made only by the use of desiccants invarious forms. The Applicant there claims to have solved this problem byfor the first time providing a seal intended to prevent penetration ofmoisture into the inhaler, particularly into the storage container of apowder inhaler with in particular elastic sealing elements.

To this end, reference is made to sealing elements made from “allconventionally known materials, for example natural or synthetic rubber,a silicone or PTFE” and like materials.

Subsequently, with reference to the “Clickhaler” powder inhaler fromInnovata Biomed, an arrangement is described in detail which concerns aparticular arrangement of the metering mechanism of this inhaler, whichcomprises a metering device in the manner of a star feeder in the formof an inclined truncated cone.

In the embodiment described, the sealing element provided is a likewisefrustoconical sealing sleeve which is fitted over the truncated meteringcone and is intended to be pivotable, so that it can assume a sealingposition and a non-sealing position. Here, page 5 interestinglydescribes how this sealing sleeve is preferably to be made of asynthetic material like that of the metering cone. It is furtherproposed that the sealing sleeve be provided with the same number ofholes as the metering cone element has metering cavities. The sealingsleeve and the metering element are to be designed in such a way that,when both are turned, a metering chamber formed by an opening in thesealing sleeve first takes up the medicament from the reservoir andthen, upon further turning, deposits this in the metering cavity in theactual metering cone and is finally conveyed from there into an airchannel.

A particularly advantageous embodiment is described in which the outercontour of the sealing sleeve forms a spherical section and provides agood fit with a corresponding curvature of the medicament storage space.The inner contour of the sealing sleeve is intended to be adapted to thefrustum of the metering cone.

From U.S. Pat. No. 6,132,394 A, it is known to provide, in a medicamentchamber of an inhaler, a separate container containing a desiccant. Thisis described as differing from U.S. Pat. No. 4,274,403 A in that acompletely closed separate container is used which is made of a materialwhich is as far as possible permeable to moisture and in which thedesiccant, for example silica gel, is to be placed. An importantadvantage of this is stated to be the fact that, compared toconventional dry capsules, there are no assembly or connection pointsthrough which small amounts of the desiccant can pass into themedicament chamber and thus contaminate the powdered medicament. Inconventional dry capsules, such connection points are to be present inparticular between capsule body and porous membrane through which thewater vapour is to pass into the desiccant.

The separate container is accordingly intended to be made as far aspossible from a single material, preferably one with a high degree ofwater vapour permeability. Suitable materials proposed are polycarbonate(PC) and ABS (acrylonitrile-butadiene-styrene). The drying behaviourover a relatively long period of time is intended here to be adapted viathe material of the container.

WO 01/46038 discloses the use of a stopper, a foil, a tablet or a liningof an EVA copolymer with 35-80% by weight of a desiccant such as silicagel, clay or zinc chloride as desiccant capsule or embedded in a storagecontainer in particular for packaged foods, mention being made ofdeficient mechanical stability of the stopper etc., and the risk ofmechanical decomposition at relatively high concentrations of desiccant.Here, the EVA types described as being suitable have quite highproportions of vinyl acetate copolymers, so that these materials havevery high water vapour permeability.

WO 01/21238 discloses a powder inhaler with hermetic sealing when not inuse. To this end, in the case of a powder inhaler with a medicamentstorage space and with an air channel running through under the storagespace, a sealing skirt is provided on each side of the storage containerand covers an air inlet opening and an inhalation opening of the airchannel in a position of rest. When an actuating cap is actuated to movea metering plunger through the storage space in order to convey a doseof medicament from the reservoir into the air channel, the two sealingskirts secured on the actuating cap are moved downwards too until themetering plunger has reached its emptying position. Through-holes areprovided in the sealing skirts and are arranged in such a way that, withthe actuating cap in the end position, they free the openings of the airchannel. As long as the actuating cap is kept depressed, the air can besucked through the air channel. When the actuating cap is released andreturns to its starting position, the openings of the air channel areclosed again.

By means of an additional guide arrangement and an elastic design of thesealing skirts, these are pressed against the outer wall in order toincrease the sealing effect. In this arrangement, as the distancetravelled from the opening position to the closing position increases,the sealing skirts are pressed increasingly more strongly against theouter wall of the inhaler transverse to the direction of movement. Anelastic seal in the form of a bellows is also provided between actuatingcap and inhaler housing in order to close the gap between saidstructural parts.

SUMMARY OF THE INVENTION

The object of the invention is therefore to improve known systems foradministering powdered pharmaceuticals.

According to the invention, this object is achieved by means of apharmaceutical powder cartridge for powder inhalers for holding apharmaceutical depot for a large number of pharmaceutical powder doses,having at least one storage space and an integrated metering device,said integrated metering device comprising at least one metering slidewhich can be moved approximately transversely in a metering slidechannel at least from a filling position to an emptying position,approximately transversely with respect to the direction of flow of thepharmaceutical powder out from the at least one storage space, themetering slide channel with the at least one metering slide being sealedoff from the environment at least in the filling position of themetering slide.

By means of the design according to the invention, and for only theslightest additional outlay, an effective protection of thepharmaceutical storage space against moisture from the environment isobtained, in particular during intermediate storage during the period ofuse after the patient has begun using the storage space. This advantageapplies both while the pharmaceutical cartridge is fitted in an inhalerand also when it is being stored outside the inhaler. Compatibility withknown powder inhalers for exchangeable pharmaceutical powder cartridgesof the type mentioned at the outset can be maintained.

In a particularly preferred embodiment, a pharmaceutical powdercartridge according to the invention is characterized in that themetering slide channel has, at one end, an opening to the environmentthrough which a part of the metering slide can pass, and, around theopening, a contact surface is provided for a seal.

A particularly reliable function can be achieved if the metering slidehas a sealing surface provided in a plane approximately transverse toits direction of movement from the filling position to the emptyingposition. In this way, it is at the same time possible to avoid a changeof frictional forces during the movement of the metering slide which, inknown inhalers, can be caused by a movement of the seal along thesealing surface, by powder residues or wear of the seal.

Particularly reliable sealing is achieved if said sealing is provided byan elastic seal.

In the case of prolonged storage prior to the pharmaceutical powdercartridge being inserted into an inhaler, an especially permanent andeffective sealing is guaranteed if the metering slide can further bemoved into an additional storing position and the seal is elasticallyprestressed sealingly at least in the storing position of the meteringslide, especially if the metering slide is fixed in the storing positionby resiliently elastic means.

In a preferred embodiment, a pharmaceutical powder cartridge accordingto the invention is characterized in that the metering device comprisesat least one metering cavity for holding a predetermined quantity of apharmaceutical powder.

For administering active substance combinations, it can also beadvantageous if the pharmaceutical powder cartridge has at least twostorage spaces, in particular if the pharmaceutical powder cartridge hasa metering device, said metering device having, for each of the storagespaces, a metering cavity for apportioning a predetermined quantity ofeach medically active substance provided in the storage spaces.Depending on the active substance combination provided, it is alsoadvantageous if the metering devices of the individual pharmaceuticalpowder cartridges have metering cavities of identical or differentvolume.

A particularly economical application, especially suitable for expensivepharmaceutical powders with only occasional administration, is possibleif the pharmaceutical powder cartridge further has a device forindicating the quantity of pharmaceutical doses which remain in thestorage chambers or which have been removed from the storage chambers.

The advantages of the invention can be used especially in long-term useof a pharmaceutical powder cartridge for powder inhalers for holding apharmaceutical depot for a large number of pharmaceutical powder doses,having at least one storage space and an integrated metering device,said integrated metering device being able to assume at least a fillingposition and an emptying position and being able to move from thefilling position to the emptying position, and with a seal beingprovided which substantially seals off the storage space from theenvironment and against entry of moisture, at least in the fillingposition of the metering device, said seal being elastically deformable,during a movement of the metering device from its emptying position toits filling position, without any sliding movement of the seal relativeto the sealing surfaces.

In a preferred embodiment of the invention, the seal is made of asilicone rubber or an elastomer, more preferably a thermoplasticelastomer, preferably of TPEE (thermoplastic polyester elastomer).

The improvement in the application properties afforded by the invention,particularly through actively reducing the effect of moisture on apharmaceutical powder during the period of use by a patient or ahospital establishment, is further achieved by means of a pharmaceuticalpowder cartridge for powder inhalers or a powder inhaler having at leastone storage space for holding a pharmaceutical depot for a large numberof pharmaceutical powder doses, including a housing body and a lid whichsubstantially enclose the at least one storage space, and where thehousing body and/or the lid are made predominantly of a PVDC(polyvinylidene chloride), a pharmaceutically compatible plastic coatedcompletely or partially with PVDC, an olefin copolymer with heterocyclicside groups (COC or mPP), or a PCTFE (polychloro-trifluoroethylene).

In a particularly advantageous embodiment, a pharmaceutical powdercartridge according to the invention is characterized in that at leastone metering slide as a component of the metering device is madepredominantly of a PVDC (polyvinylidene chloride), a pharmaceuticallycompatible plastic coated completely or partially with PVDC, an olefincopolymer with heterocyclic side groups, an at least partially orientedPP (polypropylene) or a PCTFE (polychloro-trifluoroethylene).

To limit the effects of moisture, which has penetrated into thecartridge or is present therein, on a pharmaceutical powder, it isfurther expedient if a pharmaceutical powder cartridge for powderinhalers or a powder inhaler according to the invention is characterizedin that the housing body and/or lid comprises, on at least part of theside facing the storage space, a blend of desiccant embedded in athermoplastic matrix.

To avoid impairment of the pharmaceutical by desiccant residues, it isadvantageous, according to the invention, to provide a pharmaceuticalpowder cartridge for powder inhalers or a powder inhaler having at leastone storage space for holding a pharmaceutical powder depot for a largenumber of pharmaceutical doses, containing at least one shaped body madeof a blend of a thermoplastic matrix with a desiccant embedded therein,preferably silica gel, bentonite or molecular sieve, particularly ifchannels are formed in a matrix of a thermoplastic of low waterabsorption, as are obtainable by dissolving soluble co-extrudatecomponents. For rapid uptake of residual moisture in the storage space,it can also be expedient in this case if fibres which absorb watervapour are embedded as filler in a matrix of a thermoplastic of lowwater absorption.

It is particularly advantageous, for economic mass production, if theblend in a matrix of a thermoplastic of low water absorption and adesiccant embedded therein is designed at least as part of an inner wallof a storage space by multi-component injection-moulding in a housingbody made of a plastic substantially impermeable to water vapour.

Within the meaning of the invention, it is further advantageous ifhousing body and lid are sealed watertight, preferably by ultrasonicwelding.

For particularly economic production, the seal is co-injected onto thehousing body or the metering slide.

The invention can be advantageously exploited in economic terms using aninhaler for powdered pharmaceuticals with a pharmaceutical powdercartridge according to the invention, and with an inhaler for powderedpharmaceuticals, in which the pharmaceutical can be taken by a patientby way of an air stream, characterized by a holder for a pharmaceuticalpowder cartridge according to the invention.

The advantages of the invention are particularly beneficial for patientsrequiring treatment with a pharmaceutical powder cartridge according tothe invention containing a powder with one or more of the followingactive substances: analgesics, anti-allergics, antibiotics,anticholinergics, anti-histamines, anti-inflammatory substances,antipyretics, corticoids, steroids, antitussives, bronchodilators,diuretics, enzymes, substances acting on the cardiovascular system,hormones, proteins and peptides.

APPLICATION OF THE INVENTION

By means of the invention, it is possible to make availablepharmacodynamically active substances in the form of powderedpharmaceuticals over a long period of use, even when they are sensitiveto moisture or are under unfavourable climatic conditions, and in sodoing also to obtain the advantages of re-usable inhalers withexchangeable pharmaceutical powder cartridges.

It is also possible to make available powdered pharmaceuticals forinhalation in different active substance combinations under improvedstorage conditions, of which individual active substances have increasedsensitivity to moisture affecting their storage life, their stability ortheir dosability. Active substances for which the invention can be usedcan also be for example from the group of beta-sympathomimetics:salbutamol, reproterol, fenoterol, formoterol, salmeterol. Possibleexamples from the group of corticosteroids are: budesonide,beclomethasone, fluticasone, triamcinolone, loteprednol, mometasone,flunisolide, ciclosonide. Possible examples from the group ofanticholinergics are: ipatropium bromide, thiotropium bromide,glycopyrrolate.

Possible examples from the group of analgesics and anti-migraines are:morphine, tramadol, flupirtine, sumatryptan. The following can be usedfor example from the group of peptides and proteins: cetrorelix,insulin, calcitonin, parathyroid hormone, factor VIII analogs,interferon alpha, interferon beta, heparin, FSH (follicle-stimulatinghormone), colistin, tobramycin.

Use is not limited to the active substances mentioned here. Thepharmaceutical powder cartridge described is suitable for all activesubstances which can be metered in powder form and administered byinhalation. By appropriate modification of the system and of themetering device, the invention described is also suitable forcombination of active substances which contain liquid formulations, forexample solutions or suspensions of pharmacodynamically activesubstances.

Pharmaceutical powder formulations which can expediently be used withthe pharmaceutical powder cartridge system according to the inventioncan contain various active substances, such as, for example, analgesics,anti-allergics, antibiotics, anticholinergics, antihistamines,anti-inflammatory substances, antipyretics, corticoids, steroids,antitussives, bronchodilators, diuretics, enzymes, cardiovascularagents, hormones, proteins and peptides. Examples of analgesics arecodeine, diamorphine, dihydromorphine, ergotamine, fentanyl andmorphine; examples of anti-allergics are cromoglycinic acid andnedocromil; examples of antibiotics are cephalosporins, fusafungine,neomycin, penicillins, pentamidine, streptomycin, sulphonamides andtetracyclines, colistin, tobramycin; examples of anticholinergics areatropine, atropine methonitrate, ipratropium bromide, oxitropiumbromide, trospium chloride and thiotropium bromide; examples ofantihistamines are azelastine, flezelastine and methapyrilene; examplesof anti-inflammatory substances are beclomethasone, budesonide,loteprednol, dexamethasone, flunisolide, fluticasone, tipredane,triamcinolone, mometasone; examples of antitussives are narcotine andnoscapine; examples of bronchodilators are bambuterol, bitolterol,carbuterol, clenbuterol, ephedrine, epinephrine, formoterol, fenoterol,hexoprenaline, ibuterol, isoprenaline, isoproterenol, metaproterenol,orciprenaline, phenylephrine, phenylpropanolamine, pirbuterol,procaterol, reproterol, rimiterol, salbutamol, salmeterol, sulfonterol,terbutaline and tolobuterol; examples of diuretics are amiloride andfurosemide; an example of an enzyme is trypsin; examples ofcardiovascular agents are diltiazem and nitroglycerin; examples ofhormones are cortisone, hydrocortisone and prednisolone; examples ofproteins and peptides are cyclosporine, cetrorelix, glucagon andinsulin. Further active substances which can be used are adrenochrome,colchicine, heparin, scopolamine. The active substances listed by way ofexample can be used as free bases or acids or as pharmaceuticallyacceptable salts. Counterions which can be used include, for example,physiological alkaline earth metals or alkali metals or amines, forexample acetate, benzene sulphonate, benzoate, hydrogen carbonate,hydrogen tartrate, bromide, chloride, iodide, carbonate, citrate,fumarate, malate, maleate, cluconate, lactate, pamoate and sulphate.Esters can also be used, for example acetate, acetonide, propionate,dipropionate, valerate.

The invention also allows the doctor to very accurately adapt the doseto the patient over a long period of time, without the need to disposeof partially emptied cartridges, which would have a disadvantageouseffect on treatment costs, and without compromising compatibility withother cartridges with different metering devices, e.g. with thecartridge known from WO 97/00703.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a pharmaceutical powder cartridge according to theinvention, in a perspective view;

FIG. 2 shows a plan view of a seal of a pharmaceutical powder cartridgeaccording to the invention;

FIG. 3 shows a view of a carrier mechanism of a metering slide in apharmaceutical powder cartridge according to the invention;

FIG. 4A shows a view of a metering slide body in a pharmaceutical powdercartridge according to the invention;

FIG. 4B shows a longitudinal section through the metering slide body ofa pharmaceutical powder cartridge according to the invention from FIG.4A;

FIG. 5 shows a longitudinal section through a pharmaceutical powdercartridge according to the invention, in an inhaler with the meteringslide in the emptying position; and

FIG. 6 shows a longitudinal section through a pharmaceutical powdercartridge according to the invention, in an inhaler with the meteringslide in the filling position.

DESCRIPTION OF PREFERRED ILLUSTRATIVE EMBODIMENTS

FIG. 1 shows a perspective view of a housing body 11 of a pharmaceuticalpowder cartridge 1 according to the invention for exchangeable insertioninto a powder inhaler 2. The pharmaceutical powder cartridge 1 shownhere has, at the upper area of its housing body 11, an edge 3 whichincludes two grip areas 4 in order to permit easy insertion of thepharmaceutical powder cartridge 1 into a powder inhaler 2. In theillustrative embodiment shown, a device for indicating the amount ofpharmaceutical doses which remain in the storage space 6 or have beenremoved from the storage space 6 is provided at the same time in theedge 3, in an annular channel 5 formed therein (the device is not shownin detail however), for example in the form of foil strips withcorresponding markings as is described in detail in WO 97/00703. Theuser can then read off the markings through the viewing window 7 in theedge 3.

The edge 3 also serves to receive a lid 8 with which the storage space 6forming the main part of the pharmaceutical powder cartridge 1 can besealed off. Such a lid 8 is expediently sealed in a watertight manner toa collar 10 formed within the edge 3, for example by ultrasonic welding.

Arranged below the storage space 6 there is a metering slide channel 12in which a metering slide acting as metering device is movably arranged,which metering slide, in the illustrative embodiment described here, ismade up of three parts, namely a carrier 13, the actual metering slidebody 14, and a seal 15 (FIGS. 2, 3, 4A and 4B). The metering slide isconfigured in such a way that the seal 15 shown in FIG. 2 is insertedinto the carrier 13 shown in FIG. 3 and the carrier 13 is clipped withseal 15 onto the metering slide body 14.

As can be clearly seen from FIG. 1, the metering slide channel 12 at oneend has an opening 16 and, formed around the opening 16, there is acontact surface 17 for the seal 15 of the metering slide. The contactsurface 17 is at the same time provided as a sealing surface and extendsin a plane approximately perpendicular to the direction of movement ofthe metering slide from a filling position, as is shown in FIG. 6, to anemptying position, as is shown in FIG. 5.

The metering slide body 14 shown in FIGS. 4A and 4B comprises a meteringcavity 18 whose holding volume represents the dose quantity to be madeavailable for an inhalation. The seal 15 can for example be co-injectedin multi-component injection-moulding and for this purpose can be made,for example, of a thermoplastic elastomer.

Correspondingly, a sealing surface can be provided on the metering slideand the elastic seal 15 can be mounted or better still injection-mouldedin the area of the opening 16 of the metering slide channel 12.

The housing body 11 and/or the lid 8 and/or the metering slide body 14can advantageously be made of a COC by injection-moulding. A suitablematerial with the name TOPAS® 8007 is commercially available as a trialproduct from the company Ticona in Germany.

For pharmaceutical combinations in which the powders cannot be stored,or cannot adequately be stored, as a mixture, it can also be expedientto provide two storage chambers instead of the one storage-space 6.

FIGS. 5 and 6 show a longitudinal section through the pharmaceuticalpowder cartridge 1 inserted into an inhaler 2. As can be seen from thefigures, the metering slide, designated overall by 9, can move in themetering slide channel 12 at least from the filling position shown inFIG. 6 to the emptying position shown in FIG. 5.

In the filling position shown in FIG. 6, pharmaceutical powder can fallfrom the storage space 6 into the metering cavity 18. When the meteringcavity 18 has been filled, as desired, with a pharmaceutical powder, themetering slide 9 can be moved to the emptying position shown in FIG. 5with the aid of engagement means in a powder inhaler which are onlyindicated schematically here, for example such as those described inU.S. Pat. No. 5,840,279 A, and which cooperate with the carrier 13.

The emptying position is reached when the metering cavity 18 is situatedover an emptying opening 19. When the metering slide 9 has reached thisposition, the pharmaceutical powder can fall from the metering cavity 18through the emptying opening 19, for example into a powder channel 20 ofan inhaler 2.

The filling position of the metering slide 9 can be seen clearly in FIG.6, with the metering cavity 18 under a hole 21 on the underside of thestorage space 6. To reach the empting position, the metering slide 9 ispushed to the left in FIG. 6 until this metering cavity 18 covers theemptying opening 19 and the pharmaceutical powder can fall down from it.

It can also be clearly seen in FIG. 6 that the seal 15 of the meteringslide 9 lies on the contact surface 17 of the metering slide channel 12and ensures a good sealing, preferably with slight elastic deformation.This can be done by prestressing with resiliently elastic means, inparticular via an actuating device in the inhaler for the metering slide9, which expediently also effects an immediate reverse movement of themetering slide 9 from the emptying position, as shown in FIG. 5, to itssealed filling position, as shown in FIG. 6, as soon as a pharmaceuticaldose has been removed.

For a higher contact pressure of the seal 15 of the metering slide 9 onthe contact surface 17 of the metering slide channel 12, and thus for aparticularly reliable sealing during storage of a pharmaceutical powdercartridge according to the invention, especially prior to its first usein a powder inhaler, it is advantageous to provide, slightly further tothe right in the view in FIG. 6, an additional storing position for themetering slide 9 of a filled pharmaceutical powder cartridge 1 in whichthe metering slide 9 can be fixed by the releasable snap connection 22shown. In this storing position, the seal 15 of the metering slide 9 onthe contact surface 17 of the metering slide channel 12 is subject to anincreased prestressing force.

In the upper area of the storage space there is also advantageously ashaped body 23 which is preferably secured in its position viacorresponding shaped edges 24, in order to avoid mechanical loading ofthe pharmaceutical powder. The shaped body 23 is expediently produced byinjection-moulding from a blend of a thermoplastic matrix and adesiccant. The desiccant is intended in particular to absorb moisturewhich is situated in the storage space 6 or which has penetrated throughthe metering cavity 18. The use of such a shaped body 23 ensures that nocrumbs of the desiccant, typically silica gel, can pass into thepharmaceutical powder and thus into the airways of a patient. Such ashaped body can be made of a PP matrix which itself does not take upwater and which is injected mixed with a water-soluble compound and thedesiccant, for example polyethylene glycol, and the water-solublecompound is then washed out. This results in a sponge-like structurewith channels which, after the shaped body has dried, permit rapid waterabsorption of the (not water-soluble) silica gel through large surfacesusing capillary condensation.

In order to obtain a rapid water absorption in the whole shaped body 23,it may also be expedient to embed suitable fibres as filler in the blendof desiccant and thermoplastic matrix, which fibres, by means of theircapillary action, ensure rapid transport of the air moisture and of thewater to the desiccant.

The shaped body 23 can also be designed in the form of a wall lining inthe manner of an insert, as is shown purely by way of example in FIG. 5,or, by multi-component injection-moulding in the production of thepharmaceutical powder cartridge, can form all or part of an inner wallof the storage space 6.

1. A pharmaceutical powder cartridge removably insertable into a powderinhaler, said cartridge having a storage space defining a pharmaceuticaldepot for holding a large number of pharmaceutical powder doses, saidcartridge including a housing body defining said storage space and a lidfor substantially enclosing said storage space, said cartridge furtherincluding a metering device, said metering device including a meteringslide channel and a metering slide received within said metering slidechannel and defining a dosing cavity, said metering slide movable withinsaid metering slide channel between a filling position in which saiddosing cavity of said metering slide is in communication with saidstorage space and a dispensing position in which said dosing cavity ofsaid metering slide is not in communication with said storage space,said cartridge further including a single elastic seal member, said sealseparate from and in abutment with said metering slide, said seal memberpreventing moisture from the environment from entering the storage spacewhen the metering slide is in said filling position; wherein saidmetering slide channel is defined by a pair of opposing parallel wallsand said metering slide is received between and slidable with respect tosaid walls, and said seal member engages said pair of opposing parallelwalls when said metering slide is in said filling position and does notengage said pair of opposing parallel walls when said metering slide isin said dispensing position.
 2. The cartridge of claim 1, in combinationwith at least one powdered pharmaceutical contained within said storagespace.
 3. The cartridge of claim 1, wherein said lid ispermanently_secured to said housing body.
 4. The cartridge of claim 1,wherein said metering device further comprises a sealing member, saidsealing member in engagement with said housing when said metering deviceis in said filling position.
 5. The cartridge of claim 4, wherein saidmetering device further comprises a latch member initially retainingsaid metering device in said filling position with said sealing memberin engagement with said housing.
 6. The cartridge of claim 1, wherein atleast one of said housing body and said lid made predominantly from oneof a polyvinylidene chloride, a pharmaceutically compatible plasticcoated completely or partially with polyvinylidene chloride, an olefincopolymer with heterocyclic side groups, and apolychlorotrifluoroethylene.
 7. The cartridge of claim 1, wherein saidmetering slide is linearly movable in a direction transverse to alongitudinal axis of said cartridge.
 8. The cartridge of claim 1,wherein said seal member is an annular member.
 9. A pharmaceuticalpowder cartridge removably insertable into a powder inhaler, saidcartridge having a storage space for holding a pharmaceutical depot forstoring a large number of pharmaceutical powder doses, said cartridgehaving a shaped body made from a porous matrix of an injection-moldedblend of a thermoplastic and a silica gel desiccant, said silica geldesiccant embedded within said matrix, said cartridge having a hole onthe underside of said storage space for delivering the pharmaceuticalpowder from within the storage space, said cartridge further including aseparate single elastic seal member, said seal member separate from saidbody and said storage space and disposed beneath said underside of saidstorage space, said seal member preventing moisture from the environmentfrom entering the storage space through the hole; wherein said meteringslide channel is defined by a pair of opposing parallel walls and saidmetering slide is received between and slidable with respect to saidwalls, and said seal member engages said pair of opposing parallel wallswhen said metering slide is in said filling position and does not engagesaid pair of opposing parallel walls when said metering slide is in saiddispensing position.
 10. The cartridge of claim 9, in combination withat least one powdered pharmaceutical contained within said storagespace.
 11. The cartridge of claim 9, further comprising a lid, said lidpermanently secured to a housing body of said cartridge.
 12. Thecartridge of claim 9, wherein said body further includes a meteringdevice, said metering device including a metering slide channel and ametering slide received within said metering slide channel and defininga dosing cavity, said metering slide movable within said metering slidechannel between a filling position in which said dosing cavity of saidmetering slide is in communication with said storage space and adispensing position in which said dosing cavity of said metering slideis not in communication with said storage space.
 13. The cartridge ofclaim 12, wherein said metering device further comprises a sealingmember, said sealing member in engagement with said housing when saidmetering device is in said filling position.
 14. The cartridge of claim13, wherein said metering device further comprises a latch memberinitially retaining said metering device in said filling position withsaid sealing member in engagement with said housing.
 15. The cartridgeof claim 9, wherein said seal member is an annular member.